The presence of melatonin rhythmicity in the retina of mammals has been demonstrated by several in vivo and in vitro studies, but many aspects of its synthesis and regulation in this tissue are still obscure. The goals of the present research proposal are to identify the cell type(s) that synthesizes melatonin and to elucidate the role of environmental light and of the circadian clock in regulating melatonin synthesis in the retina of mammals. The first specific aim will test the hypothesis that cone photoreceptors contain the melatonin synthesizing machinery as well as the circadian clock components to regulate it. The second aim will test the hypothesis that rod photoreceptors and/or inner retinal neurons contain the circadian clock(s) that drives retinal melatonin biosynthesis in cones. Finally, the third aim will test the hypothesis that cone photopigments mediate the suppression of retinal melatonin that follows exposure nocturnal exposure to light. In our research we will use a wide array of new and technologically advanced techniques such as dual in situ hybridization, quantitative real time PCR and Laser Capture Dissecting Microscopy. Retinal melatonin is involved in the modulation of several aspects of retinal physiology; thus the understanding of how this hormone (neuromodulator) is regulated will likely improve our understanding of retinal physiology and pathologies. Modem life style has tremendously changed our daily exposure to light and darkness and thus it is important to understand the effect that such exposure may have on the organism and, in particular, retinal function.